Incorporation of labelled carbohydrates into thyroglobulin has been recently investigated by the principal investigator, in collaboration with Dr. J. Robbins, during his stay at the CEB of the NIAMDD. It has been demonstrated that in an experimental rat thyroid tumor thyroglobulin (TG) synthesis is impaired because of a defective incorporation of sialic acid into TG. The impaired synthesis is due to a deficiency of the membrane-bound sialyltransferase that is accompanied by a defective TG secretion. The aim of the proposed project is to investigate the incorporation of carbohydrates into thyroglobulin in human tumor and in congenital hypothyroid goiter in order to establish if the observed decreased amount of soluble iodoproteins in these pathological conditions could be due to a defective carbohydrate incorporation into the thyroglobulin molecule. Slices of human congenitally goitrous and tumor thyroid tissue as well as normal thyroid for comparison will be incubated with labelled carbohydrates and the soluble and the particulated proteins, solubilized by detergents, will be characterized by analyzing the physiochemical parameters (sedimentation coefficient, electrophoretic mobility in disc gel), and the immunochemical properties (immunodiffusion, immunoelectrophoresis, double immunoprecipitation). The identification of the labeled products will be carried out by chromatography for neutral sugar and hexosamines. We will correlate the biochemical data with the morphological data obtained by light and electron-microscopic autoradiography. Autoradiography studies will be carried out with the labeled carbohydrates to establish the site of incorporation of each sugar and their correlation with the secretion of TG.